Is It Safe To Stay On TRT For Life? Long-Term Risks

For men with diagnosed testosterone deficiency, TRT is often a long-term treatment, and the safety of staying on it indefinitely is one of the most common questions providers hear. The short answer: the largest cardiovascular safety trial to date was not associated with an increase in major heart events over a mean follow-up of 33 months (Lincoff et al., 2023). That finding prompted the FDA to remove its previous cardiovascular boxed warning from all testosterone products in February 2025 (FDA, 2025). But "safe" doesn't mean "without risks," and it doesn't mean monitoring is optional.

Long-term TRT can be safe when prescribed for confirmed hypogonadism, managed by a licensed clinician, and paired with regular lab work. Marek Health provides telehealth evaluations and ongoing monitoring for men on testosterone replacement therapy. The difference between safe long-term TRT and risky long-term TRT comes down to oversight: consistent bloodwork, honest risk conversations, and dose adjustments based on individual lab results.

Testosterone replacement therapy (TRT) is the medical use of exogenous testosterone to treat men with symptomatic hypogonadism confirmed through repeated lab testing and clinical evaluation per AUA diagnostic criteria (Mulhall et al., 2018). TRT is FDA-approved only for hypogonadism caused by a medical condition, not for age-related decline alone.

What Did the TRAVERSE Trial Find?

The TRAVERSE trial is the largest randomized, placebo-controlled study designed to test the cardiovascular safety of TRT (Lincoff et al., 2023). It enrolled 5,246 men ages 45-80 with diagnosed hypogonadism and preexisting or high-risk cardiovascular disease.

After a mean follow-up of 33 months, the rate of major adverse cardiovascular events was similar between the testosterone and placebo groups, meeting the trial's prespecified noninferiority threshold. TRT was not associated with a statistically significant increase in major cardiovascular events in this high-risk population (Lincoff et al., 2023).

That said, TRAVERSE was not a blanket safety pass. The testosterone group had higher rates of atrial fibrillation, pulmonary embolism, and acute kidney injury compared to placebo. No increase in prostate cancer was observed (Lincoff et al., 2023). The trial used transdermal gel over a mean treatment period of roughly 22 months, and the FDA has extended its labeling conclusions to all testosterone formulations, including injectables (FDA, 2025). Longer-term data beyond the trial's follow-up period are not yet available, and individual risk profiles may change over time.

The February 2025 FDA labeling update removed the boxed cardiovascular warning that had been on all testosterone products since 2015, and added a new warning about blood pressure increases (FDA, 2025). The Limitation of Use statement was retained: testosterone is not approved for low levels caused solely by aging.

How TRT Affects the Body Over Years

When exogenous testosterone enters the body, the hypothalamic-pituitary-gonadal (HPG) axis detects sufficient circulating testosterone and reduces its own signaling. The brain's hormonal signals to the testes decline, and with them, the body's own testosterone production and sperm output.

This suppression is a predictable effect of exogenous testosterone on the HPG axis, and something providers discuss before starting treatment. For men who remain on TRT, testicular function stays suppressed as long as exogenous testosterone continues. The clinical question isn't whether suppression happens, but whether the benefits of correcting the deficiency outweigh the trade-offs, and whether monitoring catches problems before they become serious.

Over months and years, TRT may support improvements in energy, body composition, libido, and mood in men with confirmed deficiency. These associations are documented in clinical literature, though individual responses vary and depend on adherence, dosing, and the underlying cause of the deficiency (Bhasin et al., 2018).

Risks That Require Ongoing Monitoring

TRT carries real risks that don't disappear with time. Regular lab work is what makes long-term use manageable.

Elevated red blood cell concentration is the most common lab change on TRT. Testosterone stimulates red blood cell production (erythropoiesis), and levels can rise above the normal range. A 2025 retrospective study found that a meaningful proportion of men on TRT developed elevations requiring clinical attention (Neidhart et al., 2025). Both the Endocrine Society and AUA guidelines recommend dose adjustment or therapeutic phlebotomy (Bhasin et al., 2018; Mulhall et al., 2018).

Blood pressure now carries an FDA-level warning. The 2025 labeling update added a specific caution about blood pressure increases with testosterone use, making periodic blood pressure checks part of the standard monitoring protocol (FDA, 2025).

Estrogen-related changes occur because a portion of testosterone converts to estrogen through aromatase activity. Elevated estrogen levels can contribute to fluid retention, mood changes, and gynecomastia. Monitoring estrogen levels helps providers adjust treatment before symptoms develop (Bhasin et al., 2018).

The Endocrine Society recommends routine bloodwork during the first year of treatment and at regular intervals afterward, with the schedule guided by the prescribing provider (Bhasin et al., 2018). Sleep apnea is another consideration. The guideline lists untreated severe obstructive sleep apnea as a relative contraindication to starting TRT. Other contraindications that a provider evaluates before prescribing include certain active cancers and conditions that may worsen with testosterone use.

Does TRT Suppress Fertility?

Exogenous testosterone suppresses spermatogenesis in most men. The degree and duration of suppression vary. Some men become azoospermic (zero sperm count) on TRT, while others retain reduced sperm production. The AUA guideline recommends discussing fertility goals before starting treatment (Mulhall et al., 2018).

Recovery of spermatogenesis after stopping TRT is variable, not guaranteed. Some men recover sperm production within months, while others take longer or don't fully recover. Adjunct medications like hCG (human chorionic gonadotropin) may support fertility preservation during TRT, though these are used off-label.

For men who know they want children, providers may recommend alternatives like enclomiphene, which may support testosterone levels while preserving the body's own hormonal signaling. This is a conversation to have before starting TRT, not after.

What Happens When Men Stop TRT?

Discontinuing TRT is possible, but natural testosterone production doesn't return immediately. The HPG axis has been suppressed by exogenous testosterone, and restarting endogenous production takes time.

Recovery timelines depend on how long a man was on TRT, his age, the underlying cause of hypogonadism, and whether he had meaningful natural production before starting. Recovery prospects vary depending on the underlying cause of hypogonadism, and a provider can assess individual likelihood based on clinical history.

During the transition, symptoms of low testosterone may return. Providers sometimes use recovery protocols that include hCG or other medications to stimulate the HPG axis during discontinuation. This requires lab monitoring and clinical oversight, not abrupt cessation.

Why Most Men Continue TRT

Most men who start TRT for confirmed deficiency stay on it long-term. The reason is practical: TRT addresses the deficiency, and stopping typically means symptoms of the underlying condition return. This is comparable to thyroid hormone replacement for hypothyroidism. The underlying condition persists regardless of treatment duration.

Clinical guidelines don't set a maximum duration for TRT. The Endocrine Society guideline frames it as ongoing therapy for symptomatic deficiency, with periodic reassessment of benefits, risks, and the client's goals (Bhasin et al., 2018). The decision to continue or discontinue is between the client and their provider, informed by lab data and symptom response.

Men also stay on TRT because they notice what happens when levels drop. Fatigue, reduced libido, and changes in body composition may return. That direct experience, combined with measurable lab confirmation, drives most of the continuity.

Staying Safe on Long-Term TRT

The safety of long-term TRT depends almost entirely on monitoring. Unmonitored TRT carries risks that monitored TRT can catch early and address. A licensed clinician managing testosterone replacement should be checking labs at regular intervals, adjusting doses based on individual bloodwork, and asking about symptoms at each follow-up.

Men considering long-term TRT should confirm that their provider follows guideline-based monitoring (regular bloodwork, blood pressure checks, and symptom review) and that they have a plan for fertility if relevant. TRT is a Schedule III controlled substance, and a valid prescription requires a clinical evaluation, lab confirmation, and a legitimate medical purpose.

The evidence from TRAVERSE and the 2025 FDA labeling update provides a more reassuring safety profile than what existed five years ago. For men with confirmed low testosterone and symptoms that affect daily life, continuing TRT long-term can be a medically appropriate decision when made in partnership with a qualified provider and supported by ongoing monitoring. The question, is it safe to stay on TRT for life, depends on individual factors, consistent oversight, and a shared decision between client and provider.

Disclaimer: This blog post is intended for informational purposes only and should not be considered medical advice. Always consult a healthcare professional before making changes to your health routine.

FAQs

Does long-term TRT increase the risk of a heart attack?

The TRAVERSE trial, the largest cardiovascular safety trial of TRT to date, was not associated with an increase in major adverse cardiovascular events (MACE) over a mean follow-up of 33 months. The FDA removed its cardiovascular boxed warning from all testosterone products in February 2025 based on this data. Higher rates of atrial fibrillation and pulmonary embolism were observed, which is why ongoing monitoring remains standard.

How often should men on TRT get blood work?

The Endocrine Society recommends routine bloodwork during the first year of starting TRT, then periodically based on clinical judgment. Blood pressure should also be monitored per the 2025 FDA labeling update. Your provider will determine the frequency based on your individual lab trends and symptoms.

Can men have children while on TRT?

TRT suppresses sperm production in most men, and the degree of suppression varies. The AUA guideline recommends discussing fertility goals before starting TRT. Adjunct medications like hCG may help preserve fertility during treatment, though recovery of spermatogenesis after stopping TRT is variable and not guaranteed.

What happens to hematocrit on long-term TRT?

Testosterone stimulates red blood cell production. A 2025 study found that a meaningful proportion of men on TRT developed red blood cell elevations above clinical thresholds. Guidelines recommend dose adjustment or therapeutic phlebotomy when levels reach a point the provider considers clinically significant.

Is TRT safe for men over 60?

The TRAVERSE trial enrolled men ages 45-80 with cardiovascular risk factors, and its neutral MACE finding applied across this age range. The Endocrine Society recommends individualizing the decision for older men, weighing symptom burden against personal risk factors. TRT is not indicated for age-related testosterone decline alone.

Is it safe to stay on TRT for life without a doctor?

No. TRT involves a Schedule III controlled substance that requires a valid prescription, clinical evaluation, and lab confirmation. Unmonitored use carries risks that lab-guided care can prevent, including dangerously elevated red blood cell levels and undetected blood pressure changes. Guideline-based monitoring is what separates safe long-term TRT from risky self-treatment.

References

• FDA Drug Safety Communication, February 2025

• Front Endocrinol. 2025;15:1496906

• J Clin Endocrinol Metab. 2018;103(5):1715-1744

• J Urol. 2018;200(2):423-432

• N Engl J Med. 2023;389:107-117